This is a phase I/II trial of an oral agent known as DFMO for treatment of high-grade squamous intraepithelial lesion. Since the only current treatment option for HSIL is surgical, the availability of an oral agent would represent an advance in therapy if it is effective. In addition, since the lesions are often multi-focal, systemic therapy offers a second major advantage. We therefore propose a study design in which we will enroll 14 subjects initially, study them on DFMO for six months, and perform anoscopy at defined intervals to determine if they have shown signs of disease progression or regression. After six months therapy will be discontinued and they will be followed for another period of twelve months off therapy. If anyone of the initial fourteen subjects shows signs of disease remission, then another eleven subjects will be enrolled for a total of 25 subjects. The availability of the GCRC will be essential to the successful completion of these studies, since all the necessary equipment is already there and subjects are accustomed to using the facility as part of the follow-up in other studies.